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publicado em 03/07/2011 às 13h00:00
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Cellular mechanism that reverses gene silencing is a target for anticancer therapy

Protein that helps repair DNA also participates actively in the process of demethylation, which is essential to prevent tumors

 
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Scientists at Fox Chase Cancer Center have discovered a new mechanism used by cells to activate silenced genes. This process is critical in preventing cancer, suggesting the possibility of new treatments that can tackle global characteristics of the disease. The process investigated by Professor Alfonso Bellaco and his colleagues is called methylation. In it the cell silences the gene by adding a chemical compound known as methyl group, without which the gene remains active.

According Bellac, methylation is a fundamental part of the normal gene regulation. However, when it silences the genes that normally suppress tumors, eventually causing cancer. In fact, some cancer drugs are working from the demethylation, or removing methyl groups from DNA. These drugs act specifically, causing side effects and other problems.

Now the researchers presented the first direct evidence that demethylation may be in fact an active process, controlled by a specific protein. They found that a protein called thymine DNA glycosylase (TDG), which helps repair DNA, is also responsible for removing methyl groups from DNA. Studies with mice that had no activity indicated that the TDG gene was necessary for survival. Looking more closely at the mouse embryos that did not survive, they found that methylation was all done incorrectly: genes that normally would not have been demethylated, and remained silent.

The TDG need a second protein to the DNA demethyl. Since we know that there are proteins that actively affect demethylation, then we can imagine a new kind of cancer therapy that desmethyl specific genes. We would have a kind of therapy more precise and targeted. What is also exciting is the discovery that the cell normally uses tools that fix the DNA to a very different purpose: to reverse gene silencing by demethylation. The concept that DNA repair has this additional feature is totally new again, says Bellaco.

In addition to cancer, this knowledge can also be applied to other diseases with abnormal methylation. Bellaco cautions, however, that scientists have not figured out how to target therapy to specific genes, then any benefits of this discovery are still far from reality.

detalhes Read more about this research (in English).

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Source: Isaude.net
   Palavras-chave:   Thymine DNA glycosylase    Gene silencing    Demethylation    Methylation    Cancer development    DNA repair    Methyl group   
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